This invention relates to methods and compositions for treating dermatitis.
Dermatitis is a chronic inflammatory skin disorder characterized generally by redness, edema, oozing, crusting, scaling, and pruritus. Dermatitis and eczema are often used synonymously and are used synonymously herein, including the claims.
Various types of dermatitis have been classified including contact dermatitis, atopic dermatitis, seborrheic dermatitis (dandruff), nummular dermatitis, pompholyx, psoriasis, generalized exfoliative dermatitis, stasis dermatitis, and localized scratch dermatitis. See, The Merck Manual of Diagnosis and Therapy, 16th Edition, Merck and Co. Inc., pp. 2407-2415. As utilized herein, the various types of dermatitis are collectively referenced simply as xe2x80x9cdermatitis.xe2x80x9d
Atopic dermatitis is a chronic inflammatory skin disorder exhibited by individuals with a hereditary predisposition of a lowered cutaneous threshold to pruritis. Atopic dermatitis is often accompanied by allergic rhinitis, hay fever, and asthma. A primary characteristic of atopic dermatitis is extreme itching, leading to repeated scratching which in turn results in the typical lesions of eczema. Infantile eczema occurs predominantly on the cheeks, which may extend to other areas of the body. Eczema occurring on children, adolescents, and adults is found predominantly on the flexural surfaces, especially on the antecubital and popiteal areas, and on the neck, eyelids, wrists, and behind the ears.
In atopic dermatitis, and eczema in general, immunologically mediated leukocyte infiltration (particularly infiltration of mononuclear cells, lymphocytes, neutrophils, and eosinophils) into the skin significantly contributes to the pathogenesis of these diseases. Chronic eczema also is associated with significant hyperproliferation of the epidermis.
Atopic dermatitis and eczema, if sufficiently severe, can lead to death. Less serious, but uncomfortable and often painful symptoms associated with atopic dermatitis include itching, swelling, redness, blisters, crusting, ulceration, pain, scaling, cracking, hair loss, scarring, or oozing of fluid involving the skin, eye or mucosal membranes.
The need to control atopic dermatitis has led to a search for therapeutic agents that are both safe and effective. Corticosteroids, when administered systemically, are effective in this regard but are associated with significant and potentially dangerous side effects. Topically applied corticosteroids have some efficacy in treating these conditions, but are only partially effective in many instances and have their own significant side effects, including atrophy of tissue, formation of telangiectasia, blanching, and a myriad of systemic effects if significantly absorbed. Other agents with partial utility for treating some of the above conditions include psoralen plus ultraviolet A (PUVA), cyclosporin A, ultraviolet A (UVA) and topical Doxepin, for treatment of the associated symptom of pruritis. However, the risk-to-benefit ratios for these agents are unfavorable for most of the conditions described above.
As a result, there is a significant and very long-standing need to identify new agents with favorable benefit to risk ratios that can be applied topically to prevent, suppress or control atopic dermatitis and its associated symptom of (pruritis).
The invention is directed to the administration of xcex945-androstene-3xcex2-ol-7,17 dione and metabolizable precursors thereof, such as xcex945-androstene-3xcex2-acetoxy-7,17 dione, to treat dermatitis and the associated symptom of pruritis.